Comparison of quantitative whole body PET parameters on [68Ga]Ga-PSMA-11 PET/CT using ordered Subset Expectation Maximization (OSEM) vs. bayesian penalized likelihood (BPL) reconstruction algorithms in men with metastatic castration-resistant prostate cancer.

BACKGROUND: PSMA PET/CT is a predictive and prognostic biomarker for determining response to [177Lu]Lu-PSMA-617 in patients with metastatic castration resistant prostate cancer (mCRPC). Thresholds defined to date may not be generalizable to newer image reconstruction algorithms. Bayesian penalized likelihood (BPL) reconstruction algorithm is a novel reconstruction algorithm that may improve contrast whilst preventing introduction of image noise. The aim of this study is to compare the quantitative parameters obtained using BPL and the Ordered Subset Expectation Maximization (OSEM) reconstruction algorithms. METHODS: Fifty consecutive patients with mCRPC who underwent [68Ga]Ga-PSMA-11 PET/CT using OSEM reconstruction to assess suitability for [177Lu]Lu-PSMA-617 therapy were selected. BPL algorithm was then used retrospectively to reconstruct the same PET raw data. Quantitative and volumetric measurements such as tumour standardised uptake value (SUV)max, SUVmean and Molecular Tumour Volume (MTV-PSMA) were calculated on both reconstruction methods. Results were compared (Bland-Altman, Pearson correlation coefficient) including subgroups with low and high-volume disease burdens (MTV-PSMA cut-off 40 mL). RESULTS: The SUVmax and SUVmean were higher, and MTV-PSMA was lower in the BPL reconstructed images compared to the OSEM group, with a mean difference of 8.4 (17.5%), 0.7 (8.2%) and - 21.5 mL (-3.4%), respectively. There was a strong correlation between the calculated SUVmax, SUVmean, and MTV-PSMA values in the OSEM and BPL reconstructed images (Pearson r values of 0.98, 0.99, and 1.0, respectively). No patients were reclassified from low to high volume disease or vice versa when switching from OSEM to BPL reconstruction. CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/CT quantitative and volumetric parameters produced by BPL and OSEM reconstruction methods are strongly correlated. Differences are proportional and small for SUVmean, which is used as a predictive biomarker. Our study suggests that both reconstruction methods are acceptable without clinical impact on quantitative or volumetric findings. For longitudinal comparison, committing to the same reconstruction method would be preferred to ensure consistency.

Development of a Visually Calculated SUVmean (HIT Score) on Screening PSMA PET/CT to Predict Treatment Response to 177Lu-PSMA Therapy: Comparison with Quantitative SUVmean and Patient Outcomes.

177Lu-PSMA therapy is an effective treatment in patients with metastatic castration-resistant prostate cancer. SUVmean is a valuable screening biomarker to assess the suitability for 177Lu-PSMA therapy but requires quantitative software. This study aims to develop a simple, clinically applicable prostate-specific membrane antigen PET/CT score that encompasses the elements of SUVmean without requiring additional quantification. Methods: Datasets from ethics-approved trials of patients with metastatic castration-resistant prostate cancer after androgen receptor signaling inhibition and taxane chemotherapy (or unfit for taxane), who were treated with 177Lu-PSMA-617 and 177Lu-PSMA I&T with a pretreatment screening with 68Ga-PSMA-11 PET/CT, and clinical outcome data, including a prostate-specific antigen (PSA) 50% response rate (PSA50), PSA progression-free survival (PSA-PFS), and overall survival (OS), were included. The screening 68Ga-PSMA-11 PET/CT of all participants was analyzed both semiquantitatively and visually. Semiquantitative analysis was used to derive the SUVmean Visual analysis of the 68Ga-PSMA-11 PET/CT images involved a binary visual heterogeneity assessment (homogeneous or heterogeneous), allocating a tumor SUVmax range (<15, 15-29, 30-49, 50-79, or ≥80). A 4-category score incorporating both heterogeneity and intensity of tumors (HIT) was then developed as a combination of heterogeneity and intensity (SUVmax range). The SUVmax was less than 15 for score 1, 15-79 with heterogeneous intensity for score 2, 15-79 with homogeneous intensity for score 3, and 80 or greater for score 4. This score was evaluated according to clinical outcomes (PSA50, PSA-PFS, and OS) and compared with SUVmean Results: Data from 139 participants were analyzed. In total, 75 (54%) patients achieved a PSA50 with a median PSA-PFS of 5.5 mo (95% CI, 4.1-6.0 mo) and an OS of 13.5 mo (95% CI, 11.1-17.9 mo). SUVmean was associated with PSA50 and survival outcomes when analyzed as a continuous variable or as quartiles. The PSA50 for HIT scores 1-4 was 0%, 39%, 65%, and 76%, respectively. The HIT score was strongly related to PSA-PFS and OS (log-rank test, P < 0.001 and P = 0.002). The median PSA-PFS for HIT scores 1-4 was 1.0, 4.1, 6.0, and 8.5, respectively, and the median OS was 7.6, 12.0, 18.5, and 16.9 mo, respectively. Cohen κ between readers for the HIT score was 0.71. Conclusion: A prostate-specific membrane antigen PET/CT score incorporating HIT derived from tools on a standard PET workstation is comparable with quantitative SUVmean as a prognostic tool following 177Lu-PSMA therapy.

The Prognostic Power of Preablation Stimulated Thyroglobulin in Children With Differentiated Thyroid Cancer.

OBJECTIVE: To analyze prognostic factors in children with differentiated thyroid carcinoma (DTC) who have been treated in a single center in the last 27 years. METHODS: We studied 126 children (≤18 years old) who have been treated with near-total thyroidectomy followed by radioiodine therapy and thyroid hormone replacement. Follow-up of the patients was done 2, 6, and 12 months after treatment and then by yearly evaluation. Response to treatment was defined according to the American Thyroid Association guidelines. RESULTS: Papillary thyroid cancer was the main pathology (93.7%), and 52.4% of the patients had lymph node metastasis at presentation, which was extensive (>5) in 30% of the patients. Distant metastasis was seen in 8.8%. The mean initial dose of I-131 was 74 ± 42.2 MBq/kg. The median follow-up was 59 months and the median time to achieve an excellent response was 29 months. The preablation stimulated thyroglobulin (psTg) level was 202.4 ± 301.8 ng/mL in patients with first-year incomplete response compared with 11.2 ± 17.5 ng/mL in others (P =.001). Furthermore, using logistic regression, the psTg level was found to be the only significant predictor of distant metastasis, and psTg ≥ 13.75 ng/mL was the most powerful predictor of first-year incomplete response. Moreover, distant metastasis was more common in boys than in girls, and it took longer time for boys to achieve an excellent response. CONCLUSION: The psTg level was the only significant predictor of distant metastases in children with DTC, and psTg ≥ 13.75 ng/mL was the most powerful predictor of first-year incomplete response.

How to Report PSMA PET.

Prostate cancer (PCa) is the most common cancer diagnosed in men in most developed countries and a leading cause of cancer-related morbidity and mortality. Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has become a valuable tool in the staging and assessment of disease recurrence in PCa, and more recently for assessment for treatment eligibility to PSMA radioligand therapy (RLT). Harmonization of PSMA-PET interpretation and synoptic reports are needed to communicate concisely and reproducibly PSMA-PET/CT to referring physicians and to support clinician therapeutic management decisions in various stages of the disease. Uniform image interpretation is also important to provide comparable data between clinical trials and to translate such data from research to daily practice. This review provides an overview of the value of PSMA-PET across the different clinical stages of PCa, discusses published reporting criteria for PSMA-PET, identifies pitfalls in reporting PSMA, and provides recommendations for synoptic reports.

Clinical Trial Protocol for PRIMARY2: A Multicentre, Phase 3, Randomised Controlled Trial Investigating the Additive Diagnostic Value of [68Ga]Ga-PSMA-11 Positron Emission Tomography/Computed Tomography in Men with Negative or Equivocal Multiparametric Magnetic Resonance Imaging for the Diagnosis of Clinically Significant Prostate Cancer.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has an established role for the diagnosis of clinically significant prostate cancer (sPCa). The PRIMARY trial demonstrated that [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) was associated with a significant improvement in sensitivity and negative predictive value for sPCa detection. OBJECTIVE: To demonstrate that addition of prostate-specific membrane antigen (PSMA) radioligand PET/CT will enable some men to avoid transperineal prostate biopsy without missing sPCa, and will facilitate biopsy targeting of PSMA-avid sites. DESIGN, SETTING, AND PARTICIPANTS: This multicentre, two-arm, phase 3, randomised controlled trial will recruit 660 participants scheduled to undergo biopsy. Eligible participants will have clinical suspicion of sPCa with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 2 and red flags, or a PI-RADS score of 3 on mpMRI (PI-RADS v2). Participants will be randomised at a 1:1 ratio in permuted blocks stratified by centre. The trial is registered on ClinicalTrials.gov as NCT05154162. INTERVENTION: In the experimental arm, participants will undergo pelvic PSMA PET/CT. Local and central reviewers will interpret scans independently using the PRIMARY score. Participants with a positive result will undergo targeted transperineal prostate biopsies, whereas those with a negative result will undergo prostate-specific antigen monitoring alone. In the control arm, all participants undergo template transperineal prostate biopsies. Participants will be followed for subsequent clinical care for up to 2 yr after randomisation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: sPCa is defined as Gleason score 3 + 4 (≥10%) = 7 disease (grade group 2) or higher on transperineal prostate biopsy. Avoidance of transperineal prostate biopsy will be measured at 6 mo from randomisation. The primary endpoints will be analysed on an intention-to-treat basis. CONCLUSIONS: Patient enrolment began in March 2022, with recruitment expected to take 36 mo. PATIENT SUMMARY: For patients with suspected prostate cancer who have nonsuspicious or unclear MRI (magnetic resonance imaging) scan findings, a different type of scan (called PSMA PET/CT; prostate-specific membrane antigen positron emission tomography/computed tomography) may identify men who could avoid an invasive prostate biopsy. This type of scan could also help urologists in better targeting of samples from suspicious lesions during prostate biopsies.

Predictive value and accuracy of [18F]FDG PET/CT modified response criteria for checkpoint immunotherapy in patients with advanced melanoma.

PURPOSE: Immune checkpoint inhibitors (ICIs) are widely used in metastatic melanoma and dramatically alter the treatment of these patients. Given the high cost and potential toxicity, a reliable method for evaluating treatment response is needed. In this study, we assessed tumor response in patients with metastatic melanoma treated with ICIs using three modified response criteria: PET Response Evaluation Criteria for Immunotherapy (PERCIMT), PET Response Criteria in Solid Tumors for up to Five Lesions (PERCIST5), and immunotherapy-modified PET Response Criteria in Solid Tumors for up to Five Lesions (imPERCIST5). METHODS: Ninety-one patients with non-resectable stage IV metastatic melanoma who received ICIs were retrospectively enrolled in this study. Each patient had two [18F]FDG PET/CT scans performed before and after ICI therapy. Responses at the follow-up scan were evaluated according to PERCIMT, PERCIST5, and imPERCIST5 criteria. Patients were classified into four groups: complete metabolic response (CMR), partial metabolic response (PMR), progressive metabolic disease (PMD), and stable metabolic disease (SMD). To assess the "disease control rate," two groups have been defined based on each criterion: patients with CMR, PMR, and SMD as "disease-controlled group (i.e., responders)" and PMD as the "uncontrolled-disease group (i.e., non-responders)". The correspondence between metabolic tumor response defined by these criteria and clinical outcome was assessed and compared. RESULTS: The response and the disease control rates were 40.7% and 71.4%, 41.8% and 50.5%, and 54.9% and 74.7% based on the PERCIMT, PERCIST5, and imPERCIST5 criteria, respectively. PERCIMT and imPERCIST5 showed significantly different disease control rates from that of PERCIST5 (P < 0.001), whereas it was not significant between PERCIMT and imPERCIST5. Overall survival was significantly longer in the metabolic responder groups than in the non-responder groups based on PERCIMT and PERCIST5 criteria (PERCIMT: 2.48 versus 1.47 years, P = 0.003; PERCIST5: 2.57 versus 1.81 years. P = 0.017). However, according to imPERCIST5 criterion, this difference was not observed (P = 0.12). CONCLUSION: Although the appearance of new lesions can be secondary to an inflammatory response to ICIs and indicative of pseudoprogression, given the higher rate of true progression, the appearance of new lesions should be interpreted deliberately. Of the three assessed modified criteria, PERCIMT appear to provide more reliable metabolic response assessment that correlates strongly with overall patient survival.

Comparison between viral vector and mRNA based COVID-19 vaccination in prevalence and severity of regional immune reactions, and 18F-FDG PET/CT features.

Objectives: The coronavirus pandemic caused by SARS-CoV-2 commenced in late 2019, and global wide vaccination appears to be the only reasonable solution to fight this dreadful virus. There are two main types of COVID-19 immunization using viral vector and mRNA-based vaccines. However, the impact of each of type on 18F-FDG PET/CT needs to be accurately assessed. This study aimed to compare the 18F-FDG PET/CT features of these two types of COVID-19 vaccines. Methods: A total of 188 patients referred for 18F-FDG PET/CT with a recent history of either BioNTech/Pfizer or AstraZeneca COVID-19 vaccination, and a control group of 40 patients with no history of any type of recent vaccination, were included in the study. 18F-FDG PET/CT studies of vaccinated patients assessed for injection site uptake and regional nodal and systemic reactions post vaccination. The data were compared to the control group and to the contralateral side for each patient. The findings were compared between patients who received Pfizer and AstraZeneca vaccines. Results: 18F-FDG PET/CT was semiquantitatively positive in 50.5% of the studied population for vaccine-related features. The ipsilateral axillary and infra- and supraclavicular lymph nodes were significantly larger in size and exhibited higher metabolic activity compared to the contralateral lymph nodes after both types of vaccination. The prevalence of regional nodal reactions post Pfizer and AstraZeneca vaccination was 39% and 17.9% on visual, and 61% and 47.6% on semiquantitative assessments, respectively. Patients receiving the Pfizer vaccine exhibited higher metabolic activity in the ipsilateral regional lymph nodes (p<0.05). No significant difference in the intensity of regional nodal reaction post vaccination was noted between the first four weeks. Conclusion: Significant local and regional nodal reactions are observed after both viral vector and mRNA COVID-19 vaccination with a tendency to extend toward the infra- and supraclavicular nodal stations but not to the pulmonary hilum. The greater intensity and extension of the nodal reaction after Pfizer vaccination suggests a higher possibility of false-positive results on 18F-FDG PET/CT studies using mRNA vaccination technology.

More Accurate Imaging Is Not Stage Migration: Time To Move from "Hubble" to "Webb" in Hormone-sensitive Prostate Cancer.

Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) produces strikingly superior images compared to conventional imaging, raising the important question of whether conventional imaging is sufficiently accurate to guide patient management. Reducing false positive results with consequent improvement in accuracy is not stage migration and PSMA PET/CT can be a successor to conventional imaging in the staging of metastatic hormone-sensitive prostate cancer.

The value of FDG PET/CT imaging in outcome prediction and response assessment of lymphoma patients treated with immunotherapy: a meta-analysis and systematic review.

PURPOSE: Treatment strategies of lymphoid malignancies have been revolutionized by immunotherapy. Because of the inherent property of Hodgkin lymphoma and some subtypes of non-Hodgkin lymphoma as a highly FDG-avid tumor, functional 18F-FDG PET/CT imaging is already embedded in their routine care. Nevertheless, the question is whether it is still valuable in the context of these tumors being treated with immunotherapy. Herein, we will review the value of 18F-FDG PET/CT imaging lymphoid tumors treated with immunotherapy regimens. METHODS: A comprehensive literature search of the PubMed database was conducted on the value of the 18F-FDG PET/CT for immunotherapy response monitoring of patients with malignant lymphoma. The articles were considered eligible if they met all of the following inclusion criteria: (a) clinical studies on patients with different types of malignant lymphoma, (b) treatment with anti-CD20 antibodies, immune checkpoint inhibitors or immune cell therapies, (c) and incorporated PET/CT with 18F-FDG as the PET tracer. RESULTS: From the initial 1488 papers identified, 91 were ultimately included in our study. In anti-CD20 therapy, the highest pooled hazard ratios (HRs) of baseline, early, and late response monitoring parameters for progression-free survival (PFS) belong to metabolic tumor volume (MTV) (3.19 (95%CI: 2.36-4.30)), maximum standardized uptake value (SUVmax) (3.25 (95%CI: 2.08-5.08)), and Deauville score (DS) (3.73 (95%CI: 2.50-5.56)), respectively. These measurements for overall survival (OS) were MTV (4.39 (95%CI: 2.71-7.08)), DS (3.23 (95%CI: 1.87-5.58)), and DS (3.64 (95%CI: 1.40-9.43)), respectively. Early and late 18F-FDG PET/CT response assessment in immune checkpoint inhibitors (ICI) and immune cell therapy might be an effective tool for prediction of clinical outcome. CONCLUSION: For anti-CD20 therapy of lymphoma, the MTV as a baseline 18F-FDG PET/CT-derived parameter has the highest HRs for PFS and OS. The DS as visual criteria in early and late response assessment has higher HRs for PFS and OS compared to the international harmonization project (IHP) visual criteria in anti-CD20 therapy. Early changes in 18F-FDG PET parameters may be predictive of response to ICIs and cell therapy in lymphoma patients.

Longer Time to Reach Excellent Response to Treatment in Familial Versus Sporadic Non-medullary Thyroid Cancer (NMTC): A Matched Case-Control Study.

BACKGROUND: Familial non-medullary thyroid cancer (NMTC) are supposed to be more aggressive and require more frequent treatment compared to non-familial thyroid cancer. OBJECTIVES: This matched case-control study aimed to compare the response to treatment between the matched case-control groups of familial and sporadic NMTC. METHODS: This is a retrospective study in patients with familial NMTC (at least one other first-degree relative involved) who were treated with surgery, followed by radio-iodine therapy (RIT) without consideration of its familial origin. Response to treatment was compared between familial NMTC and age, sex, and TNM stage-matched non-familial NMTC (control group). Response to treatment was assessed one and two years after RIT, and time to excellent response was identified. RESULTS: Out of 2,944 NMTC patients, 81 (2.75%) patients had familial NMTC. We compared 66 patients with familial NMTC and 66 sporadic NMTC patients. There was no significant difference in first thyroglobulin, initial and accumulative iodine dose, and additional treatments (additional surgery and radiotherapy) between patients and controls. Although no significant difference was noted in one and two years' responses to treatment between the case and control groups, familial NMTC patients required more time to achieve excellent response (26.7 ± 24.9 versus 15.9 ± 9.0 months, P = 0.01). No significant difference was noted between familial NMTC patients with two or more than two involved relatives. CONCLUSIONS: Our study showed that if patients with familial NMTCs were treated in the same way as non-familial patients, the time to excellent response would be significantly longer, even when they have only one other involved relative.

The value of 18F-FDG PET/CT for predicting or monitoring immunotherapy response in patients with metastatic melanoma: a systematic review and meta-analysis.

PURPOSE: To investigate the ability of 18F-FDG PET/CT to assess the response of patients with metastatic melanoma to immunotherapy. METHODS: A comprehensive search of the literature for studies examining the prognostic value of 18F-FDG PET/CT in monitoring the response of patients with metastatic melanoma to immunotherapy was performed. We also screened the references of the selected articles to identify any other relevant studies. Detailed data were extracted and categorized. Comprehensive meta-analysis software was used for analysis. RESULTS: Twenty four eligible articles were included in the systematic review. Based on the baseline 18F-FDG PET/CT imaging, the pooled hazard ratios of MTV, SLR, SUV/SULmax, SUV/SULpeak, and TLG for overall survival (OS) were 1.777 (95%CI: 1.389-2.275, p < 0.001), 3.425 (95%CI: 1.707-6.869, p = 0.001), 0.941 (95%CI: 0.599-1.477, p = 0.791), 1.704 (95%CI: 1.253-2.316, p = 0.016), and 1.755 (95%CI: 1.315-2.342, p < 0.001), respectively. The conventional and modified response assessment criteria exhibited a pooled sensitivity of 64% (95%CI: 46-79%) and 94% (95%CI: 81-99%) and a pooled specificity of 80% (95%CI: 59-93%) and 84% (95%CI: 64-95%), respectively, for the early 18F-FDG PET/CT scan. On the other hand, based on the late 18F-FDG PET/CT scan, the pooled sensitivity of 67% (95%CI: 35-90%) and 92% (95%CI: 73-99%) and pooled specificity of 77% (95%CI: 56-91%) and 76% (95%CI: 50-93%) were observed for the conventional and modified criteria, respectively. PET-detectable immune-related adverse events (irAEs) were associated with the response to therapy. CONCLUSIONS: The baseline SUVpeak, MTV, and TLG parameters represent promising predictors of the final response of metastatic melanoma patients to immunotherapy. Modified response assessment criteria are potentially an appropriate method for monitoring immunotherapy. irAEs are also valuable for predicting eventual clinical benefit of treatment.

Prognostic value and optimal threshold of first thyroglobulin in low/intermediate risk DTC.

BACKGROUND: The aim of this study was to define prognostic value and optimal threshold of first thyroglobulin (fTg) measured after thyroidectomy and just before radio-iodine therapy (RIT), in low/intermediate risk patients with differentiated thyroid cancer (DTC). METHODS: This is a retrospective study in 383 patients with DTC who were treated with surgery followed by RIT. Response to treatment was assessed 1 and 2 years after RIT. Odds ratio of different risk factors like age, sex, TNM stage, fTg and Anti-Tg Ab were compared between patients with and without incomplete response 1 and 2 years after treatment. Receiver operating curve analysis was used for definition of optimal fTg cut off for detection of incomplete response. RESULTS: 218 female and 55 male with DTC had negative anti-Tg antibody (mean age: 37.5±14.5 years) and analyzed separately. fTg≥33.5 ng/mL and fTg/TSH ratio of ≥0.36 had the optimal sensitivity and specificity for detection of incomplete response 1 and 2 years after treatment. fTg<33.5 ng/mL had NPV of 98.5% for exclusion of distant metastases. Patients with fTg≥33.5 ng/mL had longer "time to excellent response" (3.6±2.3 vs. 2.0±1.8 yrs) and needed more additional treatments compared to patients with fTg<33.5 ng/mL. Multivariate analysis showed that fTg was the most potent risk factor for prediction of treatment failure 1 and 2 years after RIT. CONCLUSIONS: fTg of ≥33.5 ng/mL was the most important risk factor for prediction of treatment failure after RIT and could be included in decision algorithms regarding intensity of treatments in low/intermediate risk patients with DTC.

Response Evaluation and Survival Prediction After PD-1 Immunotherapy in Patients with Non-Small Cell Lung Cancer: Comparison of Assessment Methods.

Immunotherapy using programmed death-1 blockers is a promising modality for non-small cell lung cancer (NSCLC). Therefore, defining the most accurate response criteria for immunotherapy monitoring is of great importance in patient management. This study aimed to compare the correlation between survival outcome and response assessment by PERCIST, version 1.0; immunotherapy-modified PERCIST (imPERCIST); RECIST, version 1.1; and immunotherapy-modified RECIST (iRECIST) in NSCLC patients. Methods: Seventy-two patients with NSCLC who were treated with nivolumab or pembrolizumab and had baseline and follow-up 18F-FDG PET/CT data were analyzed. The patients were categorized into responders (complete or partial response) and nonresponders (stable or progressive disease) according to PERCIST1 and PERCIST5 (analyzing the peak SUV normalized by lean body mass [SULpeak] of 1 or up to 5 lesions), imPERCIST1, imPERCIST5, RECIST, and iRECIST. The correlation between achieved response and overall survival (OS) was compared. Results: The overall response rate and the overall disease control rate of the study population were 29% and 74%, respectively. The OS and progression-free survival (PFS) of patients with complete and partial response were statistically comparable. The OS and PFS were significantly different between responders and nonresponders (20.3 vs. 10.6 mo, P = 0.001, for OS and 15.5 vs. 2.2 mo, P < 0.001, for PFS, respectively). Twenty-three (32%) patients with progressive disease according to PERCIST5 had controlled disease according to imPERCIST5; follow-up of patients showed that 22% of these patients had pseudoprogression. The overall incidence of pseudoprogression was 7%. The response rate was 25% and 24% according to PERCIST1 and PERCIST5 (P = 0.2) and 32% and 29% according to imPERCIST1 and imPERCIST5 (P = 0.5), respectively, indicating no significant difference between analyzing the SULpeak of only the most 18F-FDG-avid lesion and analyzing up to the 5 most 18F-FDG-avid lesions. Conclusion: The achieved response by all conventional and immunotherapy-modified methods correlated strongly with patients' survival outcome, with significantly longer OS and PFS in responders than in nonresponders according to all assessed definitions. The most 18F-FDG-avid lesion according to PERCIST and imPERCIST accurately reflects the overall metabolic response.

Effect of Different 131I Dose Strategies for Treatment of Hyperthyroidism on Graves' Ophthalmopathy.

PURPOSE: The study aims to define the effect of different dose strategies on ophthalmic complications in patients with Graves' disease (GD). METHODS: All the patients with GD and no or inactive ophthalmopathy (clinical activity score; CAS < 3) underwent Snellen chart examination, measurement of proptosis, thyroid volume, and radioactive iodine uptake, and randomized into 1 of 3 groups. In group 1, all the patients received fixed low dose (FLD) of 259 MBq of I, whereas in group 2, all the patients received fixed high dose (FHD) of 555 MBq, and in group 3, calculated dose (CD) was administered to deliver 5.55 MBq/g (thyroid weight) of I. All examinations were repeated 6 months after treatment. The measurement of thyroid function tests and clinical examination were repeated after 12 months. RESULTS: We studied 92 patients (58 female and 34 male) with mean age of 38.2 ± 12.0 years. Overall, 29, 32, and 31 patients were studied in FLD, FHD, and CD groups, respectively. The patients in CD received a mean activity of 240.5 MBq. The 3 groups were not significantly different regarding age, sex ratio, radioactive iodine uptake, smoking, visual acuity, and proptosis. The response rate 12 months after radioactive iodine therapy was 66.7%, 94.4%, and 92.9% in FLD, FHD, and CD groups, respectively (P = 0.05). Overall, CAS was increased significantly after treatment. Delta proptosis and delta CAS were increased significantly in FHD group compared with other groups (P < 0.05). The highest increment in proptosis was seen in FHD group. CONCLUSIONS: The administration of 5.55 MBq/g of I has fewer ophthalmic complications compared with high fixed dose model and is more effective than low fixed dose strategy.

Application of 99mTc-UBI 29-41 scintigraphy in knee periprosthetic infection diagnosis.

AIM: In recent years, the use of total knee arthroplasty (TKA) is considered a safe and cost-effective orthopedic procedure for alleviating the chronic pain and treatment of progressive osteoarthritis. This procedure may have some complications including periprosthetic infection as the most serious and aseptic loosening as the most common one. Differentiating between these entities is important because each has a different therapeutic approach. This study was conducted to investigate the ability of 99mTC-UBI scan to distinguish septic from aseptic loosening in a painful knee prosthesis. METHODS: 34 patients with painful knee prostheses were included. The 99mTC-UBI scan was done immediately after IV administration of 99mTC-UBI in early dynamic and 30-minute static images. Time-activity curve (TAC) was drawn for all patients and target to non-target ratio (T/NT) was calculated on 30-minute images. The final diagnosis was confirmed by surgical findings, microbiologic culture results or active clinical follow up. RESULTS: Using TAC analysis, 24 99mTC-UBI scans were considered negative and 10 positive for an infectious process. Sensitivity, specificity, negative and positive predictive values were 56 %, 80 %, 83 %, and 50 %, respectively. T/NT ratio analysis on 30-minute static images demonstrated 9 positive and 25 negative patterns, with a cut off value of 1.83 for the T/NT ratio. The sensitivity, specificity, negative and positive predictive values, and accuracy of this test modality were all 100 %. CONCLUSIONS: Our findings show 99mTc-UBI scan is an excellent clinical diagnostic test for differentiating septic from aseptic loosening of the knee prostheses with perfect sensitivity and specificity. Highly accurate results were obtained only 30 minutes after injection.

A Rare Presentation of Colorectal Cancer with Unusual Progressive Intramuscular and Subcutaneous Metastatic Spread.

Colorectal carcinoma is one of the most common causes of cancer-related death, worldwide. Recently, due to the introduction of novel imaging and therapeutic techniques, five-year survival of patients has increased. However, distant metastasis is still expected in half of the patients. Colorectal cancer tends to target the abdominal cavity, liver, lungs, and bones as the common sites of metastasis. Nevertheless, rare cases of muscle metastasis have been reported. This report presents a 23-year-old male, who despite chemotherapy, demonstrated gradual progressive disease and metastases to the submandibular region, lungs, adrenal gland as well as muscles and subcutaneous tissues. He had developed multiple asymptomatic muscular metastases metachronously over two-year time period discovered on an 18FDG-PET/CT, namely in the deltoid, external oblique abdominis, rectus abdominis, and quadriceps muscles, as well as one of the extrinsic muscles of the tongue. The presence of distant, especially extrahepatic metastasis, adversely affects the prognosis of colon carcinoma. Since limited cases of muscle metastasis have been reported in carcinoma of colon, the underlying pathophysiology, optimum treatment, and prognostic issues are yet to be substantiated.

Comparison of Treatment Response Achieved by Tablet Splitting Versus Whole Tablet Administration of Levothyroxine in Patients with Thyroid Cancer.

OBJECTIVES: TSH suppression by Levothyroxine consumption is a mainstay of thyroid cancer treatment. Tablet-splitting is a worldwide approach in dose adjustment in patients. However, it is highly recommended to evaluate the validity of tablet splitting for each distinctive drug by clinical trials before routinely using tablet halves in clinical practice. In this study we compared the effect of 150 µg dose of Levothyroxine by use of a100 and a 50 µg tablets or one and half 100 µg tablets in Differentiated thyroid cancer (DTC) patients. METHODS: One hundred DTC patients treated with one and half 100 µg Levothyroxine tablets were randomly divided into two groups. The first group continued taking medication as before and the second group received the same daily dose by taking one 100 and one 50 microgram Levothyroxine tablets. The mean changes in TSH and T3 levels and patients weight were compared between the groups. RESULTS: 91 patients completed the study. Levothyroxine consumption pattern, age, gender distribution, weight and TSH levels were comparable between groups at the beginning of the study. The mean change of body weights, serum levels of T3 and TSH showed no significant difference between groups in different time points during the study (P>0.05). CONCLUSION: This study showed similar efficacy of tablet splitting and two tablets administration for Levothyroxine; however, patients preferred two tablets at the end of the study. It can be concluded that tablet splitting can be used as an alternative way when the 50 µg tablet is not available.

The Value of Technetium-99m Labeled Alpha-Melanocyte-Stimulating Hormone (99mTc-α-MSH) in Diagnosis of Primary and Metastatic Lesions of Malignant Melanoma.

OBJECTIVES: Malignant melanoma is the most lethal type of skin cancers with unfavorable prognosis. Alpha-MSH peptide analogues have a high affinity for melanocortine-1 (MC1) receptors on melanocytes over expressing in malignant melanoma cells. Pre-clinical studies have shown promising results for radiolabeled MSH imaging in this malignancy. The purpose of this study is to assess the diagnostic value of 99mTc-α-MSH imaging in malignant melanoma. METHODS: Twenty-one patients (13 men) with pathologically confirmed malignant melanoma with or without metastatic distribution were included in this study. 740-1110 MBq 99mTc-α-MSH was injected and whole body scans were performed 20, 120 and 240 minutes post injection and were assessed both qualitatively and semi-quantitatively using target (T) to background (BG) ratio. RESULTS: The T/BG ratio for the primary tumor bed was 2.51±2.26, 2.56±2.48 and 1.92±1.79 minutes in the whole body scans 20, 120 and 240 minutes post injection, respectively. The sensitivity, specificity, negative and positive predictive values were 75%, 80%, 50% and 92% for primary lesion and 25%, 100%, 68% and 100% for distant metastasis, respectively. CONCLUSION: 99mTc-α-MSH is a newly introduced agent for diagnosis of tumoral lesions in malignant melanoma. Our study showed a high sensitivity with this modality in primary lesions as well as lymph node involvements. However the detection rate was not high in distant metastasis. The preliminary results are promising especially as a new complementary imaging method in management of malignant melanoma.

Sagliker Syndrome in a Patient with Secondary Hyperparathyroidism and Chronic Renal Insufficiency: A Case Report.

Sagliker syndrome is a rare form of renal osteodystrophy resulted from untreated secondary hyperparathyroidism. It is described by severe skeletal deformities, high level of PTH in patients with chronic renal failure, and deformed face. This paper reports a 44-year-old male patient with the mentioned characteristics. In addition to the unique clinical features, high levels of ALP and PTH hormones encouraged us to search for syndrome-like a disease, which clinically and paraclinically matched the Sagliker syndrome. This case highlights the importance of clinicians' attention for early monitoring and appropriate treatment as it is shown to be effective in preventing irreversible complications such as soft tissue and bone abnormalities and cardiovascular impairment in patients with Sagliker syndrome. Therefore, considering the syndrome is recommended as one of the diagnostic hypothesis in young patients with renal insufficiency, secondary hyperparathyroidism, and skeletal deformities.

Extraosseous Accumulation of Technetium-99m-Methyl Diphosphonate (99mTc-MDP) in a Child with ALL: A Case Report.

Extraosseous accumulation of technetium-99m-methyl diphosphonate (99mTc-MDP) on bone scan is not common. This phenomenon is often attributed to abnormality of calcium metabolism and has been reported in a variety of conditions including metabolic diseases and malignancies. A five years old boy is presented here, who was admitted to the pediatric emergency suffering from fatigue, respiratory symptoms, weight loss, intermittent fevers, anorexia, nausea and vomiting, edema of legs and abdominal distension for one month. The initial laboratory analysis revealed hypercalcemia. The patient was referred for whole body bone scan with suspicion of malignancy and bone metastasis. The bone scan revealed highly increased radiotracer uptake in both lungs in the perfusion and blood pool phases. Delayed images also showed increased activity in lungs and gastric wall. The skeleton was not seen clearly. Bone marrow aspiration was done and established the diagnosis of ALL. The patient deceased due to respiratory failure 20 days later. Diffuse lung uptake in this patient was consistent with respiratory failure and poor prognosis. It is reported that bone scan may be useful for assessment of the extent of metastatic calcification and may establish suitable management to prevent organ failure.